Implantable vital sign sensor

ABSTRACT

An implantable vital sign sensor including a housing including a first portion, the first portion defining a first open end, a second open end opposite the first end, and a lumen there through, the first portion being sized to be implanted substantially entirely within the blood vessel wall of the patient. A sensor module configured to measure a blood vessel blood pressure waveform is included, the sensor module having a proximal portion and a distal portion, the distal portion being insertable within the lumen and the proximal portion extending outward from the first open end.

CROSS-REFERENCE TO RELATED APPLICATION

This application is related to and claims priority to U.S. ProvisionalPatent Application Ser. No. 62/143,592, filed Apr. 6, 2015, entitled“IMPLANTABLE VITAL SIGN SENSOR”, and is also related to and claimspriority to U.S. Provisional Patent Application Ser. No. 62/168,754,filed May 30, 2015, entitled “IMPLANTABLE VITAL SIGN SENSOR”, the entirecontents of both of which are hereby incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

n/a

FIELD

An implantable vital signs sensor and method of implantation thereof.

BACKGROUND

Real-time monitoring of a non-ambulatory patient's vital signs istypically achieved through non-invasive methods. For example, a patientin an operating room or ICU bed may have a blood pressure monitor with acuff disposable about the upper arm; a pulse oximeter engaged around afingertip; adhesive electrodes affixed to the skin (proximate to theheart) that measure the electrocardiogram and respiratory rate/patternof respiration; an oral/aural thermometer that measures bodytemperature, and a stethoscope for monitoring heart/lung/airway sounds.These non-invasive vital signs sensors are often cumbersome andunwieldy. Patients that are hospitalized, immobilized, or stationarycommonly tolerate the inconveniences inherent in non-invasive sensors.

The real-time monitoring of an ambulatory patient's vital signs,however, is more challenging owing to the patient's mobility, and lackof supervision by hospital staff. Many patients are not compliantobtaining frequent or timely vital sign measurement using non-invasivesensors. Moreover, even when a patient is attentive to compliance, thecumbersome nature of such devices often results in patient's eitherremoving the devices or shifting the devices to a more comfortableposition, which can create artifacts, inaccurate readings, and occludeblood flow. Moreover, non-invasive devices are typically less accurateand less stable than implantable sensors.

Long-term implantable intravascular blood pressure sensors have beendevised to measure blood pressure in real-time. However, suchintravascular blood pressure sensors are prone to obstruct blood flowand cause endothelial cell injury, thrombosis, and emboli. Otherlong-term implantable blood pressure sensors are disposed around theouter diameter of an artery wall and use application to produce a robustmechanical coupling with the transducer's diaphragm. Still otherimplantable blood pressure sensors are used for short periods of time inthe operating rooms, catheterization laboratories, and ICUs of ahospital.

SUMMARY

An implantable vital signs measurement device for a patient having anartery with an arterial wall, the arterial wall having a basementmembrane, the device comprising an elongate and biodegradable housingincluding a first portion, the first portion defining a first open end,a second open end opposite the first end, and a lumen there through, thefirst portion being sized to be implanted substantially entirely withinthe arterial wall of the patient and having a length between 100-1500microns, and a second portion substantially orthogonal with the firstportion and configured to contour an exterior surface of the arterialwall when the distal end of the first portion is inserted to a positionwithin the arterial wall substantially co-planar to the basementmembrane and endothelial cells of the arterial wall. A sensor modulehaving a proximal portion and a distal portion is included, the distalportion being insertable within the lumen and the sensor module beingretainable within the first portion; at least a portion of the proximalportion is configured to seal the first open end and to provide for apredetermined insertion depth when distal portion of the sensor moduleis inserted within the lumen, the proximal portion being furtherconfigured to be pressed against the second portion of the housing whenthe distal portion of the sensor module is inserted within the lumen.The sensor module having a pressure transducer configured to measure anarterial blood pressure waveform, the sensor module having a delectablediaphragm responsive to a blood pressure waveform within the artery, thediaphragm being substantially co-planar to the basement membrane andendothelial cells of the arterial wall when the sensor module isretained within the first portion. A sensor module retaining elementcoupled to the sensor module is included, the sensor module retainingelement configured to retain the sensor module within the first portion.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the present invention, and theattendant advantages and features thereof, may be more readilyunderstood by reference to the following detailed description whenconsidered in conjunction with the accompanying drawings wherein:

FIG. 1 is a front cross-sectional view of an embodiment of implantablesensor constructed in accordance with the principles of the presentinvention;

FIG. 2 is a front cross-sectional view of the implantable sensor shownin FIG. 1 implanted within a blood vessel wall;

FIG. 3A is a side view of the implantable sensor shown in FIG. 2;

FIG. 3B is a front cross-sectional view of the implantable sensor shownin FIG. 3A;

FIG. 4 is a front cross-sectional view of the implantable sensor shownin FIG. 1 with an outer flexible stent or fabric that holds the sensoragainst the blood vessel wall and within the blood vessel wall tissue;and

FIG. 5 is a system view of exemplary implanted vital signs sensors incommunication with a watch and tablet computer.

DETAILED DESCRIPTION

As used herein, relational terms, such as “first” and “second,” “over”and “under,” “front” and “rear,” “in, within, and around” and the like,may be used solely to distinguish one entity or element from anotherentity or element without necessarily requiring or implying any physicalor logical relationship or order between such entities or elements.

Referring now to the drawings in which like reference designators referto like elements, there is shown in FIGS. 1-5 an exemplary implantablevital signs sensor device and monitoring system constructed inaccordance with the principles of the present application and designatedgenerally as “10.” As used herein the phrase “vital signs” refers tomeasurements related to a patient's, whether human or animal, basic bodyfunctions, including but not limited to, heart rate, blood pressure,blood pressure waveform, blood flow, respiratory rate, tidal volume,electrocardiogram, temperature, hemoglobin oxygen saturation, bodyposition, activity level, and related measurements. The device 10 mayinclude a housing 12 sized to be at least substantially retainedentirely within a blood vessel wall of a patient, and in particular, thewall of a vein or an artery.

The long-term implantable vital sign monitoring device 10 may monitorone or more of the following parameters in real-time to determine asignificant change from an individual patient's baseline pattern whenliving in the real-world environment: heart rate, heart rhythm, strokevolume, blood pressure, systemic vascular resistance, blood flow,myocardial contractility, valve function, cardiac timing intervals,respiratory rate, respiratory rhythm, tidal volume, hemoglobin oxygensaturation, heart sounds, lung sounds, upper airway sounds, bowelsounds, temperature, electrocardiogram (lead 2, V2, and V5), activitylevel, body position, and location on the earth. The long-termimplantable vital sign monitoring device 10 may also record one or moreof the parameters for subsequent interpretation.

For example, the housing 12 may be sized to span the wall thickness ofat least one of the internal thoracic (mammary) arterylateral thoracicartery, subscapular artery, intercostal artery, superior epigastricartery, carotid artery, aorta, renal artery, iliac artery, femoralartery, brachial artery, ulnar artery, and radial artery, which mayrange in wall thickness between approximately 100-1500 microns. Forexample, the housing 12 may be sized to span the wall thickness of atleast one of the internal thoracic vein, lateral thoracic vein, jugularvein, vena cava, axillary vein, brachial vein, iliac vein, femoral veinand a peripheral vein, which may range in wall thickness betweenapproximately 40-1000 microns. In addition, the housing 12 may be sizedto span the wall thickness of a pulmonary artery or a pulmonary vein,which may range in wall thickness between approximately 40-1000 microns.The housing 12 may be composed of biodegradable and biocompatiblematerials, such that it may degrade after a predetermined amount of timewithin the body. Alternatively, the housing 12 may be composed of abiocompatible material such as stainless steel, titanium, composite,ceramic, silicone, PTFE, PE, PVC, epoxy, or glass that does not degradeover time. The housing 12 may be smooth or textured and coated with oneor more compounds that promote the adhesion and health of the vesselwall tissue.

The housing 12 may include a first portion 14 sized to substantiallyspan the entirety of wall thickness of the artery or vein into which thehousing 12 is implanted. The first portion 14 may be substantiallycylindrical in shape and define a lumen 16 there through. For example,when inserted within the internal thoracic artery, the first portion 14may define a length of approximately between 300-600 microns and asurface area of approximately 1 mm². In other configurations, the firstportion 14 may define any hollow structure sized to substantially spanthe arterial wall thickness and provide the lumen 16 there through. Thefirst portion 14 may further define a smooth outer surface to facilitateplacement within the artery wall tissue, or alternately, may be threadedon its outer surface such that the first portion 14 may be securedwithin the artery wall tissue through rotation of the first portion 14.The first portion 14 may be adhered within the arterial wall with anadhesive, or alternatively, may include a textured surface, barbs ortines that engage the surrounding tissue. The first portion 14 furtherincludes an open first end 18 configured to be positioned immediatelyadjacent to the basement membrane and endothelial cells of the artery(tunica intima) such that the first open end 18 is not in contact withblood flowing within the artery or vein and a second open end 20opposite the first end 18. In an exemplary configuration, the distancebetween the first open end 18 and the blood stream when the firstportion 14 is implanted within the arterial wall may be approximately 5to 200 microns. In another configuration, the first open end 18 issubstantially co-planar with the basement membrane and endothelialcells. In another configuration, the first end can extend 5 to 200micrometers into the artery lumen, in contact with the flowing blood.

Attached to the second end 20 may be a second portion 22 of the housing12. The second portion 22 may be positioned substantially orthogonal tothe first portion 14 and may extend across and contour at least aportion of the outer diameter of the arterial wall. For example, thesecond portion 22 may be substantially flat, rectangular, or round inshape, or alternatively, may define a curvature substantiallycorresponding to the curvature of the outer diameter of the arterialwall such that when the first portion 14 is received within the arterialwall, the second portion 22 may be pressed against the outer diameter ofthe arterial wall. The second portion 22 may further define a flatinterior surface and a rounded or bulbous exterior surface such that thesecond portion 22 protrudes a distance away from the outer diameter ofthe artery. The distance between the first end 18 and interior surfaceof the second portion 22 may be prefabricated such that when the secondportion 22 is pressed against the arterial wall, the first end 18 isposition immediately adjacent to the basement membrane and endothelialcells. Thus, the second portion 22 is configured to operate as a stopperto facilitate the insertion of the first portion 14 to the desired depthwithin the arterial wall.

Ultrasound may be used to measure the artery wall outer diameter, wallthickness, and inner diameter to determine the appropriate length/sizeof the housing 12, the first portion 14, and the second portion 22. Inparticular, the surgeon may select from pre-fabricated bases with aparticular height of the first portion 14 and length of the secondportion 22 to accommodate differently sized arteries or veins within thesame patient or different wall thickness between different patients.

A vital signs sensor module 24 may be releasably or permanently insertedand received within at least a portion of the housing 12. For example,at least a portion of the vital signs sensor module 24 may be insertedthrough the second open end 20 into the lumen 16 of the housing 12. Themodule 24 may include a sensor housing 26 that includes one or morebiosensors, such as a force or pressure transducer, configured tomeasure one or more physiological parameters of the patient, which canbe transduced and correlated into one or more vital sign measurements.In particular, the sensor module 24 may include a pressure transducerconfigured to correlate a measured deflection of a diaphragm disposedwithin to a blood pressure measurement, as discussed in more detailbelow. The module 24 may be slideably received within the lumen 16 suchthat it is retained within the lumen 16 and within the arterial wall. Inone configuration, the module 24 includes a capillary tube 28 with anoptical fiber 30 or optical sensing mechanism 30, with a transducerdiaphragm 32 on its distal tip. For example, the capillary tube 28 mayhave an optical fiber or optical sensing mechanism 30 disposed withinthe tube 28 having a rigid, semi-flexible, or flexible diaphragm 32 atits distal end, a portion of which is received within the lumen 16 andpositioned to about the tunica intima cells of the artery proximate thefirst open end 18.

As shown in FIG. 1-2, the optical fiber 30 extends through the housing26 and extends outward from the artery in a position substantiallyparallel to the length of the artery, but may extend in any direction.In one embodiment, the optical fiber 30 is not required and an opticalsensing mechanism may be included as part of the module 24 to measurethe displacement of the diaphragm 32 with each pulse to measure theblood pressure (BP) waveform. Each pulse through the artery or vein maycause the tissue and diaphragm 32 to move inward/outward a distanceproportional to the energy of the pulse wave, which may be correlated toproduce a measurement of the BP waveform. In an exemplary configuration,the diaphragm 32 is covered only by the endothelial cells, basementmembrane, and/or a small amount of connective tissue. In oneconfiguration, embodiment has the optics and electronics housed withinthe sensor housing 26 and the capillary tube 28 and the diaphragm 32housed within lumen 16. Once implanted in the body, the basementmembrane and endothelial cells may grow from the edges of the injuredartery wall tissue, over the surface of the diaphragm 32 to produce acontinuous biocompatible/hemocompatible interface. The very thin layerof cells and/or connective tissue that may cover the outer surface ofthe diaphragm 32 may stabilize, and not affect, the measurement of theintravascular blood pressure waveform.

Examples of pressure transducers that may be included in the sensormodule 24 include those with single or multiple deflectable diaphragms32 with a Wheatstone bridge configuration, a single or multiplepiezoelectric crystal configuration, or an optical configuration thataccurately measures diaphragm 32 motion. Because the diaphragm 32 ispositioned against the tunica intima, the module 24 may produce anaccurate measurement of the intravascular blood pressure waveformwithout distortion and without compressing or flattening of the arterywall, the artery lumen, the vein wall, or the vein lumen.

After implantation, the outer surface of the diaphragm 32 may remainclean or become coated with protein, carbohydrate, lipid and othercompounds. The outer surface of the diaphragm 32 can also become coatedwith basement membrane, other connective tissue and endothelial cells.The surface of the diaphragm 32 may be textured or coated with a naturalor synthetic biomaterial to enhance the adhesion of basement membraneand endothelial cells (tunica intima). Coating the outer surface of thediaphragm 32 may change the physical characteristics of diaphragm 32motion. This coating layer (not shown) may become stable within days toweeks of implantation in the body. Thus, the implanted pressure/forcesensor remains stable over time and may require infrequentre-calibration using an external BP cuff measurement system as areference. The reference BP cuff may also contain a barometer andthermometer (measures atmospheric pressure and temperature) to enhancecalibration of the implanted BP sensor.

In other configurations, the transducer's diaphragm 32 may be positionedexterior to the arterial wall, any depth within the arterial wall, orwithin the artery lumen exposed to flowing blood. For example, a post(not shown) may be located within the flowing blood (artery lumen) witha diaphragm 32 on its distal end or on the side of the post. Theintravascular post may be inserted at a right angle to the inner wall ofthe artery (90 degrees) or any angle relative to the inner wall of theartery (+320 to 0 to −320 degrees). The module's 24 diaphragm 32 may bepositioned on the side of the post toward the flow of blood and anyposition relative to the flow of blood, (0 to 360 degrees). Theintravascular post BP sensor module 24 can also be re-calibrated using areference upper arm BP cuff. An external barometer and thermometer maybe used to measure changes in atmospheric pressure and temperature toenhance calibration accuracy of the implanted BP sensor's output signal.

The module 24 may further be configured to measure a patient's bloodpressure waveform in real-time. The waveform can be analyzed todetermine: heart rate, heart rate variability, stroke volume, strokevolume variability, myocardial contractility, vascular resistance,systolic and diastolic timing interval, aortic and mitral valvefunction, blood flow, and respiratory rate/pattern of ventilation. Forexample, the sensor modules 24 may include a processor configured tocorrelate the measured physiological parameters into a vital signsmeasurement that can be transmitted and/or stored with a memory. Themodule 24 may further include one or more additional vital signs sensorsdisposed within the housing 26 or disposed along or within otherportions of the module 24. For example, a hemoglobin oxygen saturationsensor, temperature sensor, an ECG electrode, an acoustic sensor, and anactivity sensor may be included as part of the module 24, as discussedin more detail below.

The module 24 may include a sensor module retaining element 34 disposedaround the circumference of the artery or vein. The sensor moduleretaining element 34 may include a plurality of links 36, each link 36being movably connected to an adjacent link 36 to define a partialperimeter around the artery or vein. The plurality of links 36 mayconnect to the sensor housing 26 or the second portion 22 to completelysurround the artery or vein. The movability of the links 36 allows forthe artery to pulse as blood flows through it without constricting theartery or vein and maintaining contact of the housing 26 with thearterial or venous wall. The mechanism holding the links to each otherthe sensor module and the blood vessel wall may have a small, moderate,or large degree of elasticity. The inner surface of each link 36 mayfurther define a porous/textured surface such that it may fuse with thearterial or venous wall tissue such that the arterial or venous wall andthe links 36 may move substantially simultaneously during pulsatileblood flow. The links may also have one or more through and throughopenings or channels that permit the ingrowth of vessel wall tissue andvaso-vasorum. A hemoglobin oxygen saturation sensor (pulseoximeter-SpO₂) 38 may be integrated within the body of one or more linksor the housing 26. For example, in a configuration with five links 36disposed around the circumference of the, a component of the SpO₂sensors 38 may be affixed within one or more links 36 to provide for aplurality of photoplethysmograph waveforms and SpO₂ measurements. In oneconfiguration, each link 36 has a recess (not shown) sized to receiveone of the SpO₂ sensor components, for example, the light source and/ordetector such that the only barrier between the blood flow within theartery and the SpO₂ sensor 38 is the arterial wall tissue. The pulseoximeter light source and light detector may be located on the same linkor separate links located on opposite sides of the artery. Each SpO₂sensor 38 may be in communication with the processor inside the housing28, for example, by a conductor disposed within the sensor moduleretaining element 34 connecting each SpO₂ sensor to each other and tothe processor. Optionally, other sensors, for example, an ECG sensor orother electrodes may be disposed within or around the sensor moduleretaining element 34. For example, electrodes may be disposed onopposite sides of the sensor module retaining element 34 to measure theelectrocardiogram, volume of blood flow, rate of blood flow,temperature, heart/lung sounds, respiratory rate, and pattern ofventilation.

Now referring to FIG. 4, in other configurations, the sensor housing 26may be secured to the outside wall of the artery with a flexible andelastic stent, fabric, or mesh 40 disposed within a portion of the links36. These materials may have an open structure to decrease mass andfacilitate the ingrowth of tunica adventicia and vasa vasorum. Forexample, the sensor housing 26 may be fabricated with a flexible stent40 sized to be disposed around the circumference of the artery to affixthe capillary tube 28 and transducer diaphragm 32 within the lumen 16.The stent, fabric, or mesh 40 may be non-biodegradable such that it maynot degrade overtime, or alternatively, may be biodegradable such thatover a predetermined amount of time the stent, fabric, or mesh 40 maydegrade leaving the module 24 affixed to the tunica adventicia tissueand the capillary tube 28 affixed to the artery wall tissue. The stent,fabric, or mesh may define a larger diameter to that of the module 24 tosurround the module 24 and stents 40. Surgical clips, sutures, or atissue adhesive are further contemplated to be used to secure the module24 to the artery wall tissue in combination with the stent 40 or as analternative. For example, as shown in FIG. 3B, sutures are threadthrough a portion of each link 36 and attach directly to the module 24.Each link 36 may define one or more apertures or channels through withthe sutures, belts, or stents 40 may be disposed to facilitate thesecuring the housing 26 to the arterial wall.

Referring now to FIG. 5 which illustrates the location of sensor module24 implanted around the right internal mammary artery and an additionalsensor module 42 a implanted within the subcutaneous tissue of the rightupper chest wall, and a second additional sensor module 42 b implantedwithin the subcutaneous tissue of the left upper chest wall. Each sensormodule 24, 42 a, and 42 b, can be constructed with one or multiple vitalsign sensors per module. For example, subcutaneous tissue sensor modules42 a and 42 b may include an EKG electrode, a microphone, a GPS sensor,an accelerometer, and a temperature sensor. The implanted sensors 24, 42a, and 42 b may communicate with an external controller 44 with adisplay through radiofrequency telemetry. For example, the controllermay be a Smartphone, tablet device, or smart watch, such as an iPhone®,iPad®, Apple Watch® 44 (FIG. 5), or FitBit®, with an application incommunication with a processor having processing circuitry configured tocommunicate with the implanted sensors 24, 42 a, and 42 b and displaythe measured information. In one configuration, the user may wear asmart watch with built-in wireless communication to communication withthe implanted sensors 24, 42 a, and 42 b, correlate the measured data,and display the results. The controller 44 may be used by the patientand physician to display and processes the real-time and recorded sensordata, calibrate the sensors, and troubleshoot the sensors. Thecontroller 44 may contain a barometer that measures the real-timeatmospheric pressure to produce a calibrated and accurate absolute bloodpressure measurement. The controller 44 may contain a thermometer thatmeasures the real-time atmospheric temperature to produce a calibratedand accurate absolute blood pressure measurement.

The implanted sensors 24, 42 a, and 42 b can be in communication with acharge storing device (battery) 46 implanted within the body separatefrom the sensors 24, 42 a, and 42 b or within the sensor module 24, 42a, or 42 b. The charge storing device 46 may be a hermetically sealedbattery implanted within the body in wired communication with theimplanted sensors 24, 42 a, and 42 b. The implantable battery 46 may bere-charged across the skin using an external power source by, forexample, inductive charging. In an alternate embodiment, the energy forthe implanted sensors 24, 42 a, and 42 b to function may be transmittedfrom the outside of the body through the skin and the subcutaneoustissue using electromagnetic coupling or light coupling. Transmission ofexternal power to the internal sensors 24, 42 a, and 42 b requires lowenergy and thus a short transmission distance. The external power sourcemay be located near or adhered to the skin surface for extended periodsof time to power the implanted vital sign monitoring device or rechargethe implanted battery.

The module 24 containing the blood pressure sensor may be implantedaround the internal thoracic (mammary) artery (between the3^(rd)-4^(th), 4^(th)-5^(th) or 5^(th)-6^(th) intercostal space) usinglocal or general anesthesia. That artery is located perpendicular to theribs, approximately 1 cm lateral to the sternum, and between the innerand middle intercostal muscles. In an exemplary configuration, themodule 24 may be implanted at the level of the aortic valve to minimizethe effects of body position on the arterial pressure waveform and theabsolute blood pressure measurement. In an exemplary method ofimplantation, the surgeon may use a small needle, punch or an automatedstapling device to puncture the wall of the artery or vein. In partbecause the needle may create a tapered opening in the arterial wall,the first portion 14 of the housing 12 may be inserted within theaperture created by the needle such that the first open end 18 issubstantially planar or partially recessed from the basement membraneand endothelial cells. In other configurations, the needle may pierceentirely through the wall of the blood vessel. The lumen 16 of thehousing 12 may be slid around the circumference of the needle andaffixed inside the aperture with the artery wall tissue. The capillarytube 28 of the module 24 may then be inserted within the lumen 16 of thehousing 12 for affixation within the housing 12 such that one or moretransducer diaphragms 32 may be positioned substantially coplanar withthe opening of the first end 18. The stents 40 may be positioned aroundthe outside of the artery or vein and attached to the sides of themodule 24 to secure the housing 12 within the artery wall tissue and themodule 24 to the outside of the blood vessel wall.

In an exemplary configuration of the module 24, as shown in FIG. 3, twoor more blood pressure sensor waveform transducers can be positionedaround the artery with the transducer's diaphragm 32 immediatelyadjacent to the endothelial cells. The SpO₂ sensor 38 may be configuredwith one or more light sources and light detectors external to theartery wall (tunica adventicia); opposite one another (12 o'clock and 6o'clock positions). This alignment may produce a real-timephotoplethysmography signal with a high signal-to-noise ratio andminimal motion artifact. The SpO₂ sensor's 38 light sources anddetectors may also be located within the artery wall tissue adjacent tothe endothelial cells. The external surface of the module 24 (containingthe BP sensor and SpO₂ sensor), the stents 40, and the additional sensormodules 42 a and 42 b may have a metal conducting surface, for example,an electrode that can measure the real-time electrocardiogram signal ofthe heart (ECG or EKG) and the electrical signals due to movement of thediaphragm and chest wall. The module 24 and additional sensor modules 42a and 42 b may also contain a temperature thermistor that continuouslymeasures the core or blood temperature and one or more microphones thatmonitor and record the heart sounds (phonocardiogram), lung sounds,upper airway sounds, and gastrointestinal sounds.

The measured vital signs from module 24 and/or implanted sensors 42 aand 42 b may be used to alert, diagnose, and/or treat associateddiseases or conditions that can be correlated from the measured vitalsigns. For example, measurements taken from one or more of the implantedsensors, namely, ECG, blood pressure, pulse oximeter, thermometer,microphone, accelerometer, GPS may be combined and processed inreal-time to provide diagnostic and/or therapeutic recommendationsand/or therapies to the patient. Trend data from the implanted sensorscan be combined with trend data from non-invasive sensors, for example,a scale measuring body weight and a camera capturing an image of apatient's head, neck, and torso, to provide diagnostic and/ortherapeutic recommendations and/or therapies to the patient.

In an exemplary configuration, the one or more measured vital signs maybe monitored in an ambulatory patient and displayed and/or stored on thecontroller 44 or a remote database, for example, to a physician's officeand/or a central monitoring station with real-time diagnostic algorithmsand a detailed patient electronic medical record (EMR). The measuredvital signs may then be compared against a threshold value predeterminedby the patient's physician or an algorithm based on the patient'sbaseline vital sign information. For example, based on the user'sweight, height, age, family history, medications, and medical history,and prior vital signs data, the algorithm may determine a thresholdvalue or range for one or more of the vital sign measurements that theprocessor in the controller 44 or a remote location, may compare againsteach other to determine if a medical condition exists and alert thepatient, for example, via a call, text, or alarm to the controller 44, athird-party Smartphone, or an email that summarizes the condition. Thealgorithm may trigger an event to record important vital sign sensordata and transmit the trend data to the external control module andcentral monitoring station for review and clinical analysis. Ambulatorypatients may receive audible or visual alerts and alarms when the vitalsign sensor algorithms detect a significant change in vital sign trenddata. The patient may manually enter a diary of symptoms, signs, meals,medications into the diagnostic/therapeutic software algorithms tomanage their disease with greater safety and efficacy. Clinicians at acentral monitoring system can communicate with the patient via cellphone to initiate/adjust medical therapy and summarize the effects ofthat therapy over time. Described below are several diagnosticalgorithms that may use multi-modal monitoring (trend data from morethan one vital sign sensor) to diagnose the following conditions:

Myocardial Ischemia and Myocardial Infarction—real-time monitoring ofthe ECG can be used to diagnose myocardial infarction and ischemia byanalyzing ST segment depression (horizontal or down-sloping) orelevation in relation to heart rate, BP, & activity level; new onset Qwaves; unifocal and multifocal premature ventricular contractions;premature atrial contractions; supraventricular tachycardia, atrialfibrillation, new conduction delays, and new heart block related tomyocardial ischemia, myocardial infarction and heart failure. Real-timemonitoring of the blood pressure waveform can detect changes in BP,heart rate, stroke volume, myocardial contractility, systemic vascularresistance, cardiac output, systolic/diastolic timing intervals, valvefunction, and respiratory rate that typically occur with myocardialischemia at rest and with exercise. Real-time monitoring of cardiacsounds can detect wheezing, rhales, S-3 sound, and a new murmur ofmitral/aortic valve regurgitation due to myocardial ischemia, LVdysfunction, and pulmonary edema. Real-time monitoring with a pulseoximeter may detect an acute decrease in the arterial hemoglobin oxygensaturation that may occur with myocardial ischemia at rest and withexercise. Changing from a stable to an unstable pattern would beconsidered a medical emergency requiring increased vigilance andoptimized/timely medical therapy.

Congestive Heart Failure and Pulmonary Edema—Real-time monitoring of theblood pressure waveform may be used to detect changes in myocardialcontractility, stroke volume, stroke volume variability, heart rate,heart rate variability, systolic/diastolic timing intervals, valvefunction and respiratory rate that may occur with myocardial ischemia,infarction, cardiomyopathy and heart failure. Real-time monitoring ofcardiac & lung sounds can detect wheezing, rhales, S-3 sound, and a newmurmurs due to LV dysfunction and acute pulmonary edema. Real-timemonitoring with a pulse oximeter may detect an acute decrease in thearterial hemoglobin oxygen saturation. Changing from a stable to anunstable pattern would be considered a medical emergency requiringincreased vigilance and optimized/timely medical therapy.

Hypertension (Mild, Moderate & Severe) real-time monitoring of the bloodpressure waveform pattern may be used to diagnose hypertension (mean,systolic & diastolic BP>target range for age) and determine theeffectiveness of medical/drug/device therapy. For example, a sustainedupward trend for systolic, diastolic, and mean blood pressure and/orpersistent tachycardia in relation to activity, rest, and sleep mayrequire a change in medication. Medication dose may be adjusted toreal-time BP data and trend data. Monitoring the ECG can detect theacute and chronic effects of hypertension on left ventricle wallthickness and myocardial electrical activity (LV hypertrophy with strainpattern). New onset moderate/severe hypertension or changing to anunstable BP pattern would be considered a medical emergency requiringincreased vigilance and optimized/timely medical therapy.

Atrial Fibrillation or Supraventricular Tachycardia—real-time monitoringof the ECG can diagnosis new onset or recurrent atrial fibrillationand/or supraventricular tachycardia that occurs spontaneously orsecondary to myocardial ischemia, CHF, or hypertension. Real-timemonitoring of the arterial BP waveform can detect the hemodynamicsignificant of an arrhythmia (decreased BP, stroke volume, and cardiacoutput). Monitoring the pulse oximeter during the arrhythmia can detectdecreased hemoglobin oxygen saturation due to decreased and unstableblood flow. New onset atrial fibrillation, SVT or changing to anunstable rhythm pattern would be considered a medical emergencyrequiring increased vigilance and optimized/timely medical therapy.

Acute Bronchospasm (Asthma)—Changes in the vital signs measurements maybe used to diagnose upper airway obstruction, large airway obstructionand bronchospasm (due to asthma or bronchitis) and pneumothorax.Real-time monitoring of cardiac, lung, and upper airway sounds candetect wheezing, rhales, rhonchi, increased respiratory rate/tidalvolume (minute ventilation) and prolonged exhalation (increased work ofbreathing). Monitoring the arterial BP waveform can detect increasedheart rate, increased heart rate variability, decreased stroke volume,increased stroke volume variability, and decreased cardiac output.Monitoring the ECG can detect an increased HR, decreased HR variability,arrhythmias, and acute right ventricle strain. Monitoring the pulseoximeter can detect an acute decrease in hemoglobin oxygen saturation.New onset bronchospasm with a high work of breathing and decreasedhemoglobin oxygen saturation would be considered a medical emergencyrequiring increased vigilance and optimized/timely medical therapy.

Chronic Obstructive Pulmonary Disease & Respiratory Failure—Changes inthe vital signs measurements may be used to diagnose acute respiratoryfailure and a worsening of chronic bronchitis and emphysema due to acutebronchitis or pneumonia. For example, an increase in respiratory rateand minute ventilation, coughing, wheezing, decreased hemoglobin oxygensaturation, persistent tachycardia, myocardial ischemia, right heartstrain, and elevated temperature may be indicative of such a condition.A persistently high work of breathing and decreased hemoglobin oxygensaturation would be considered a medical emergency requiring increasedvigilance and optimized/timely medical therapy.

Intestinal Diseases (Chron's Disease, Ulcerative Colitis,Diverticulitis, Ischemia)—Changes in the vital signs measurements may beused to diagnose decompensation of inflammatory bowel disease. Forexample, increased/decreased bowel sounds (motility), elevatedtemperature, tachycardia, hypotension, decreased blood flow, tachypnea,decreased hemoglobin oxygen saturation may all be indicated of such acondition.

Pulmonary Embolism—Changes in the vital signs measurements may be usedto diagnose a pulmonary embolism. For example, acute onset wheezing,increased respiratory rate, increased minute ventilation, tachycardia,atrial/ventricular arrhythmias, right ventricle strain pattern on EKG,decreased hemoglobin oxygen saturation, elevated temperature, decreasedstroke volume, decreased cardiac output, and hypotension, may beindicated of such a condition. Any pulmonary embolism would beconsidered a medical emergency requiring increased vigilance andoptimized/timely medical therapy.

Hemorrhage or Dehydration—Changes in the vital signs measurements may beused to diagnose significant dehydration due to bleeding, edema,decreased oral intake, excess urination, or diarrhea. For example,increase in heart rate, peripheral vascular resistance, respiratoryrate, minute ventilation and a decrease in stroke volume, cardiacoutput, blood pressure, blood flow, and hemoglobin oxygen saturation,may be indicated of moderate to severe blood loss and/or dehydration.

The above conditions are merely exemplary of the number of ways thevital sign measurements determined from the sensor module 24 and/oradditional sensor modules 42 a and 42 b may be measured and correlatedin real-time against a patient established threshold to either signal analert to the user, signal an alert to a medical professional (primarycare physician or central monitoring station), or record the data forfurther evaluation. For example, a patient with known atrialfibrillation may have a different blood pressure threshold valuecompared to the blood pressure of a patient without atrial fibrillation.As such, the threshold value can be programmed by the doctor into thecontroller 44 or automatically by the remote database, such that whenthat threshold value is exceeded or falls below that threshold in areal-time ambulatory setting, depending on the threshold value, an alertmay be sent to the patient, the central monitoring station, and/or thepatient's physician. Similarly, patients with other conditions may havedifferent thresholds for each vital sign measurement measured by themodule 24 and/or 42 and 42 b such that each module 24 in combinationwith the controller 44 may be personalized for each patient to providean early warning sign of an individual condition prior to an adverseevent. Alerts and alarms can be based upon a simple threshold, apredicted threshold, or based upon a model of the patient's physiology.Moreover, based on the vital signs measurements, a therapeutic algorithmmay also be used in combination with the diagnostic algorithm torecommend and/or implement therapies for the patient based on themeasured vital signs compared to the patient's individual thresholdvalues or ranges. For example, the therapeutic algorithm may operate inthe above conditions as follows:

Myocardial Ischemia—Physicians and patients currently titratemedications in response to symptoms such as “chest pain” (angina)despite the fact that greater than 80% of myocardial ischemia is silentand many “pains in the chest” are due to non-cardiac causes. Medicationsfor ischemic heart disease may be dosed once or multiple times per daybased upon quantitative vital sign data. Real-time data may be used to“recommend” an adjustment in medical therapy (nitrates, ACE inhibitors,beta blockers, calcium channel blockers, aspirin, anticoagulant, andoxygen) based on the patient's medical history and historical vitalsigns measurements. It is further contemplated that the real-time vitalsign sensor system and closed-loop therapeutic algorithms mayautomatically deliver anti-ischemia medications using drug infusionpumps and/or oxygen using an oxygen source and regulator. Real-time datamay also be used to automatically adjust electrical nerve tissuestimulation devices and cardiovascular blood pump devices that optimizeblood pressure and blood flow in a sick heart.

Congestive Heart Failure & Pulmonary Edema—Changes in the patient'svital sign pattern may be used to detect the onset of CHF and pulmonaryedema in the early stages as discussed above, such that management canoccur in the ambulatory setting; avoiding a visit to the emergency roomand admission to an intensive care unit. Real-time vital sign sensordata may be used to recommend an acute change in medical therapy(diuretics, catechamines, digitalis, nitrates, beta blockers, calciumchannel blockers, ACE inhibitors, and oxygen). It is furthercontemplated that the real-time vital sign sensor system and closed-looptherapeutic algorithms may automatically deliver medications, oxygen,pacemaker therapy, ventricular assist device therapy, and totalartificial heart therapy that may increase myocardial contractility,control HR, control BP, control blood flow, oxygen concentration, anddecrease systemic vascular resistance using drug infusion pumps andelectrical stimulation.

Hypertension—Real-time analysis of the BP waveform may calculate heartrate, heart rhythm, stroke volume, arterial blood flow, myocardialcontractility, and systemic vascular resistance. Vital sign sensor datamay be used to recommend an acute change in medical therapy (diuretics,beta blockers, alpha blockers, vasodilators, ACE inhibitors, calciumchannel blockers) and monitor the effectiveness of that medical therapy.It is further contemplated that the real-time vital sign sensor systemand closed-loop therapeutic algorithms may automatically deliveranti-hypertension medications using drug infusion pumps and electricaltherapy of nervous tissue to maintain the mean, systolic, and diastolicBP is the target range during rest, exercise, sleep, and illness.

Arrhythmia—real-time vital sign sensor data may be used to recommend anacute change in medical therapy (beta blockers, calcium channelblockers, membrane stabilizers). It is further contemplated thatreal-time vital sign sensor system and closed-loop therapeuticalgorithms may automatically deliver anti-arrhythmia medications usingdrug infusion pumps; and anti-arrhythmia electrical shock therapy usinga defibrillation shock, a cardioversion shock and/or override pacemakershocks.

Asthma—real-time vital sign sensor data may be used to recommend acutemedical therapy (oxygen, catecholamine inhaler, steroid inhaler,parenteral catecholamines). It is further contemplated that thereal-time vital sign sensor system and closed-loop therapeuticalgorithms may automatically deliver anti-inflammatory andbronchodilator medications using drug infusion pumps, oxygen using anoxygen source/regulator, and electrical stimulation of nervous tissue toreduce bronchospasm and inflammation.

Chronic Obstructive Pulmonary Disease (COPD)—real-time vital sign sensordata may be used to recommend an acute change in medical therapy(oxygen, catecholamine inhaler, steroid inhaler, parenteralcatecholamines). It is further contemplated that the real-time vitalsign sensor system and closed-loop therapeutic algorithms mayautomatically deliver anti-inflammatory and bronchodilator medicationsusing drug infusion pumps, oxygen using an oxygen source/regulator, andelectrical stimulation of nervous tissue to reduce bronchospasm andinflammation.

Chronic Intestinal Diseases—real-time vital sign sensor data may be usedto recommend an acute change in medical therapy (intravenous fluids,oxygen, steroids, anti-inflammatory). It is further contemplated thatthe real-time vital sign sensor system and closed-loop therapeuticalgorithms may automatically deliver anti-inflammatory, pro-peristalsis,or anti-peristalsis medications using drug infusion pumps.

The measured vital signs data may further be processed to determinewhether trend vital sign data is “abnormal” or “extreme” relative to amodel of a universal healthy/stable patient or adapted to an individualpatient. For example, hundreds to thousands of hours of patient vitalsign data from any one or all of the sensors may be recorded andanalyzed. Large data sets may be split into (1) training sets, (2)control sets, and (3) test sets. Clinical experts may review the trenddata and label specific patterns as “crisis events” or “error codes.”The algorithms may learn from an individual patient's physiologicalpatterns and determine when the trend data is “abnormal” or “extreme”with high sensitivity and specificity (minimal false alerts/alarms andfew missed “real” events). The real-time method may estimate the extremevalue distributions of multivariate, multimodal mixture models foranalysis of complex datasets from an array of physiological vital signsensors.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed herein above. In addition, unless mention was made above tothe contrary, it should be noted that all of the accompanying drawingsare not to scale. A variety of modifications and variations are possiblein light of the above teachings without departing from the scope andspirit of the invention, which is limited only by the following claims.

What is claimed is:
 1. An implantable vital signs measurement device for a patient having an artery with an arterial wall, the arterial wall having a basement membrane and endothelial cells, the device comprising: an elongate housing including: a first portion, the first portion defining a first open end, a second open end opposite the first end, and a lumen there through, the first portion being sized to be implanted substantially entirely within the arterial wall of the patient; and a second portion substantially orthogonal with the first portion and configured to contour an exterior surface of the arterial wall when the distal end of the first portion is inserted to a position within the arterial wall substantially co-planar to the basement membrane and endothelial cells of the arterial wall; a sensor module having a proximal portion and a distal portion, the distal portion being insertable within the lumen and the sensor module being retainable within the first portion; at least a portion of the proximal portion is configured to seal the first open end and to provide for a predetermined insertion depth when distal portion of the sensor module is inserted within the lumen, the proximal portion being further configured to be pressed against the second portion of the housing when the distal portion of the sensor module is inserted within the lumen; the sensor module having a pressure transducer configured to measure an arterial blood pressure waveform, the sensor module having a deflectable diaphragm responsive to a blood pressure waveform within the artery, the diaphragm being substantially co-planar to the basement membrane and endothelial cells of the arterial wall when the sensor module is retained within the first portion; and a sensor module retaining element coupled to the sensor module, the sensor module retaining element including a plurality of connected spaced apart links configured to surround the artery and to retain the sensor module within the first portion. 